Résumé
In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(-) on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/-) mice (6 per group) were immunized with the following antibodies (100 µg each): mouse anti-LDL(-) monoclonal IgG2b, rabbit anti-LDL(-) polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25 percent cholesterol) and then every week for 21 days. The passive immunization with anti-LDL(-) monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD), respectively) compared to control (124.9 ± 13.2 µm²). Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(-) monoclonal antibody (3.5 ± 0.70 per field x 10) compared to controls (21.5 ± 3.5 per field x 10). Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(-) in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU), the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol) and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol), and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein). In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.
Sujets)
Animaux , Femelle , Souris , Lapins , Anticorps monoclonaux/administration et posologie , Athérosclérose/thérapie , Immunisation passive/méthodes , Immunoglobuline G/administration et posologie , Lipoprotéines LDL/administration et posologie , Récepteurs aux lipoprotéines LDL/immunologie , Anticorps monoclonaux/immunologie , Athérosclérose/immunologie , Athérosclérose/métabolisme , Immunohistochimie , Fragments Fab d'immunoglobuline/administration et posologie , Fragments Fab d'immunoglobuline/immunologie , Immunoglobuline G/immunologie , Peroxydation lipidique/immunologie , Lipoprotéines LDL/immunologie , Récepteurs aux lipoprotéines LDL/métabolisme , Molécule-1 d'adhérence des cellules vasculaires/immunologieSujets)
Interactions hôte-parasite , Macrophages/parasitologie , Trypanosoma cruzi/physiologie , Adjuvants immunologiques/pharmacologie , Fragments Fab d'immunoglobuline/immunologie , Macrophages/immunologie , Macrophages/ultrastructure , Récepteurs au complément , Récepteurs immunologiques , Trypanosoma cruzi/immunologie , Trypanosoma cruzi/ultrastructureRésumé
The finding that Fab fragments of the anti-E1 Tor haemagglutinin were able to afford protection in vivo (low but significant), as well as a significant reduction in Vibrio cholerae adherence to isolated intestinal epithelial cells in-vitro, implicate that masking of these cell-bound haemagglutinin sites per se, would be sufficient to confer protection in E1 Tor cholera infection. Subsequently, the related working hypothesis that the E1 Tor cell-bound haemagglutinin is playing an adhesive role is validated. In natural immunity, it could be envisaged that antiserum to this cell-bound haemagglutinin of V. cholerae E1 Tor would be highly protective due to the synergistic effects of the dual protective mechanisms in operation at the intestinal sites viz. a masking and agglutinating phenomenon.